Atherosclerosis. 2026 Jun 11:120794. doi: 10.1016/j.atherosclerosis.2026.120794. Online ahead of print.
ABSTRACT
BACKGROUND: Contemporary guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering in patients with atherosclerotic cardiovascular disease (ASCVD), yet significant treatment gaps persist in clinical practice. We evaluated lipid-lowering therapy (LLT) use, LDL-C control, and prevelance of cardiovascular risk factors among patients with coronary artery disease (CAD), peripheral artery disease (PAD), cerebral atherosclerosis (CAS) and those with all three (polyvascular disease) using real-world data from the NIH-run All of Us Research Program.
METHODS: We analyzed electronic health records from 26,935 patients with ASCVD (CAD 21,573; PAD 4752; CAS 6864; and polyvascular 902) enrolled between 2018 and 2023. We assessed baseline LLT use, LDL-C levels, and prevalence of uncontrolled cardiovascular risk factors, defined as blood pressure ≥130/80 mmHg, hemoglobin A1c ≥ 7%, waist-height ratio (WHtR) ≥ 0.5, and current smoking. Among patients with LDL-C >70 mg/dL, we visualized risk factor intersections using Euler diagrams.
RESULTS: Despite high statin use across all cohorts (81% CAD, 82% PAD, 83% CAS, 93% Polyvascular), only 36-47% achieved LDL-C <70 mg/dL and 22-31% had LDL-C ≥100 mg/dL. Combination LLT was markedly underutilized (10-21%), with ezetimibe prescribed in 10-20% and PCSK9 inhibitors in only 1-3% of patients. Among those with LDL-C ≥70 mg/dL, central obesity was ubiquitous (86-89%), more than half had uncontrolled blood pressure (59-63%), 16-26% had hemoglobin A1c ≥ 7%, and 14-20% were active smokers. Patients with polyvascular disease had higher LLT use and LDL-C control but lower risk factor control. Uncontrolled risk factors frequently co-occurred: 29-31% had concurrent obesity and uncontrolled hypertension, and 7-9% harbored the triad of obesity, poor glycemic control, and uncontrolled hypertension.
CONCLUSIONS: In this large, diverse cohort of patients with ASCVD, substantial gaps persist in achieving guideline-recommended LDL-C targets and controlling cardiovascular risk factors. The marked underutilization of combination LLT and the high coexistence of metabolic risk factors represent significant opportunities for treatment intensification and comprehensive risk factor management.
PMID:42270564 | DOI:10.1016/j.atherosclerosis.2026.120794